Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL-37: a cathelicidin found in human leukocytes and epithelium

The bactericidal activity of synthetic LL-37, a cathelicidin, was assessed against Actinobacillus actinomyoetemcomitans (three strains) and Capnocytop haga spp. (three strains). All strains were sensitive to LL-37, and exhibit ed 99% effective dose of 7.5-to-11.6 mu g/ml. An amidated form of LL-37, pe ntamide-37, killed with about the same efficacy as LL-37. Partial inhibitio n of killing was noted at physiologic concentrations of NaCl, and complete inhibition was observed at 400 mM NaCl. At approximately the 99% effective dose - i.e., 10 mu g/ml - LL-37 also lost activity against A. actinomycetem comitans in the presence of native or heat-inactivated 10-15% normal human AB serum. Pentamide-37 was less sensitive to serum inhibition than LL-37. I n conclusion, certain oral, gram-negative bacteria are sensitive to the bac tericidal activity of LL-37 at low concentrations of serum and salt, a cond ition likely to be found within the membrane-delimited phagolysosome. Modif ied forms of LL-37, such as pentamide-37, may be more suitable for future t herapeutic application in the presence of serum.